Implication of CXCR2-Src axis in the angiogenic and osteogenic effects of FP-TEB.

Application of tissue-engineered bones (TEBs) is hindered by challenges associated with incorporated viable cells. Previously, we employed freeze-drying techniques on TEBs to devitalize mesenchymal stem cells (MSCs) while preserving functional proteins, yielding functional proteins-based TEBs (FP-TEBs). Here, we aimed to elucidate their in vivo angiogenic and osteogenic capabilities and the mechanisms. qPCR arrays were employed to evaluate chemokines and receptors governing EC migration. Identified C-X-C chemokine receptors (CXCRs) were substantiated using shRNAs, and the pivotal role of CXCR2 was validated via conditional knockout mice. Finally, signaling molecules downstream of CXCR2 were identified. Additionally, Src, MAP4K4, and p38 MAPK were identified indispensable for CXCR2 function. Further investigations revealed that regulation of p38 MAPK by Src was mediated by MAP4K4. In conclusion, FP-TEBs promoted EC migration, angiogenesis, and osteogenesis via the CXCR2-Src-Map4k4-p38 MAPK axis.

An AIE-based ratiometric fluorescent probe for highly selective detection of H2S in plant stress responses.

Hydrogen sulfide (H2S) has emerged as a crucial signaling molecule in plant stress responses, playing a significant role in regulating various physiological and biochemical processes. In this study, we report an aggregation-induced emission (AIE)-based ratiometric fluorescent probe TPN-H2S for the highly selective detection of H2S in plant tissues. The probe exhibited excellent sensitivity and selectivity towards H2S over other analytes, enabling real-time monitoring of H2S dynamics in living cell. Furthermore, the AIE-based ratiometric probe TPN-H2S allowed for accurate quantification of H2S levels, providing valuable insights into the spatiotemporal distribution of Cys metabolism produces H2S. Importantly, the physiological pathways and signaling mechanisms of H2S production of was investigated in plant tissues under Cr and nano-plastics stress. Utilizing a high-throughput screening approach, we identified exogenous substances such as calcium chloride (CaCl2) and abscisic acid (ABA) that could induce higher level of H2S production during the stress response in plants. Overall, those findings demonstrate the potential of the AIE-based ratiometric fluorescent probe TPN-H2S as a powerful tool for unraveling the role of H2S in plant stress responses and pave the way for further exploration of H2S-mediated signaling pathways in plants.

Corrigendum: Frontier and hotspot evolution in cerebrotendinous xanthomatosis: a bibliometric analysis from 1993 to 2023.

[This corrects the article DOI: 10.3389/fneur.2024.1371375.].

[Recharge Sources and Hydrochemical Evolution Mechanism of Surface Water and Groundwater in Typical Karst Mining Area].

To study the recharge source, hydrochemical characteristics, and evolution process of karst underground water and surface water in the Xianghualing Mining area, we collected 32 groups of samples from karst underground water and surface water sources in and around the mining area. Based on multivariate statistical analysis, the Piper three-line diagram, Gibbs diagram, and ion ratio coefficient, this study analyzed the hydrogeochemical characteristics of karst underground water and surface water in the Xianghualing Mining area. The study systematically revealed the recharge source, recharge age, and hydrochemical evolution law of both water sources. The results showed that the karst underground water and surface water in the Xianghualing Mining area were weakly alkaline, with the main anions being HCO3- and the main cations being Ca2+. The hydrochemical types mainly included HCO3-Ca, HCO3-Ca·Mg, and HCO3·SO4-Ca·Mg types. Atmospheric precipitation was the primary source of recharge for karst underground water and surface water, and it was also influenced by evaporation during the runoff process. However, the evaporation effect of karst groundwater was relatively small, which was closely related to modern hydrology, and the cycle replacement process was more rapid. The hydrochemical evolution characteristics of karst underground water and surface water were mainly affected by rock weathering, cation exchange adsorption, mineral dissolution, and human activities （such as agricultural and mining activities）. Ca2+, Mg2+, and HCO3- were primarily derived from the dissolution of carbonate minerals, with a small portion also originating from the weathering and dissolution of silicate minerals. Na+ and Cl- were primarily derived from the dissolution of rock salts. Among them, Cl-, NO3-, and SO42- were greatly affected by external inputs from agricultural activities, domestic sewage discharge, and mining activities. The research results are of great significance to the cyclical evolution process of karst underground water and surface water, as well as the protection and utilization of water resources in the Xianghualing Mining area.

Population-based prevalence of self-reported pediatric diabetes and screening for undiagnosed type 2 diabetes in Chinese children in years 2017-2019, a cross-sectional study.

Background: The worldwide geographical and temporal variation in the prevalence of diabetes represents a challenge, but also an opportunity for gaining etiological insights. Encompassing the bulk of East Asians, a large and distinct proportion of the world population, China can be a source of valuable epidemiological insights for diabetes, especially in early life, when pathophysiology begins. We carried out a nationwide, epidemiological survey of Prevalence and Risk of Obesity and Diabetes in Youth (PRODY) in China, from 2017 to 2019, to estimate the population-based prevalence of diagnosed pediatric diabetes and screen for undiagnosed pediatric type 2 diabetes (T2D). Methods: PRODY was a nation-wide, school population-based, cross-sectional, multicenter survey by questionnaire, fasting urine glucose test and simple oral glucose tolerance test (s-OGTT), among a total number of 193,801 general-population children and adolescents (covered a pediatric population of more than 96.8 million), aged 3-18, from twelve provinces across China. The prevalence of the self-reported pediatric diabetes, the proportion of subtypes, the crude prevalence of undiagnosed T2D and prediabetes in general juvenile population and the main risk factors of type 1 (T1D) and type 2 (T2D) diabetes had been analyzed in the study. Findings: The prevalence of all self-reported pediatric diabetes was estimated at 0.62/1000 (95% CI: 0.51-0.74), with T1D at 0.44/1000 (95% CI: 0.35-0.54) and T2D at 0.18/1000 (95% CI: 0.13-0.25). For undiagnosed T2D, the crude prevalence was almost ten-fold higher, at 1.59/1000, with an estimated extra 28.45/1000 of undiagnosed impaired glucose tolerance (IGT) and 53.74/1000 of undiagnosed impaired fasting glucose (IFG) by s-OGTT screening. Maternal diabetes history is the major risk factors for all subtypes of pediatric diabetes in China. Interpretation: The PRODY study provides the first population-based estimate of the prevalence of pediatric diabetes China and reveals a magnitude of the problem of undiagnosed pediatric T2D. We propose a practical screening strategy by s-OGTT to address this serious gap. Funding: The National Key Research and Development Programme of China, Key R&D Program of Zhejiang, the National Natural Science Foundation of China and the Zhejiang Provincial Key Disciplines of Medicine, Key R&D Program Projects in Zhejiang Province.

Aquaporin CmPIP2; 3 links H2O2 signal and antioxidation to modulate trehalose-induced cold tolerance in melon seedlings.

Cold stress severely restricts the growth and development of cold-sensitive crops. Trehalose (Tre), known as the 'sugar of life', plays key roles in regulating plant cold tolerance by triggering antioxidation. However, the relevant regulatory mechanism remains unclear. Here, we confirmed that Tre triggers apoplastic hydrogen peroxide (H2O2) production and thus plays key roles in improving the cold tolerance of melon (Cucumis melo var. makuwa Makino) seedlings. Moreover, Tre treatment can promote the transport of apoplastic H2O2 to the cytoplasm. This physiological process may depend on aquaporins. Further studies showed that a Tre-responsive plasma membrane intrinsic protein 2; 3 (CmPIP2; 3) had strong H2O2 transport function and that silencing CmPIP2; 3 significantly weakened apoplastic H2O2 transport and reduced the cold tolerance of melon seedlings. Yeast library and protein-DNA interaction technology were then used to screen two Tre-responsive transcription factors, abscisic acid responsive element (ABRE)-binding factor 2 (CmABF2) and abscisic acid responsive element (ABRE)-binding factor 3 (CmABF3), which can bind to the ABRE motif of the CmPIP2; 3 promoter and activate its expression. Silencing of CmABF2 and CmABF3 further dramatically increased the ratio of apoplastic H2O2/cytoplasm H2O2 and reduced the cold tolerance of melon seedlings. This study uncovered that Tre treatment induces CmABF2/3 to positively regulate CmPIP2; 3 expression. CmPIP2; 3 subsequently enhances the cold tolerance of melon seedlings by promoting the transport of apoplastic H2O2 into the cytoplasm for conducting redox signals and stimulating downstream antioxidation.

Krüppel-like factors family in health and disease.

Krüppel-like factors (KLFs) are a family of basic transcription factors with three conserved Cys2/His2 zinc finger domains located in their C-terminal regions. It is acknowledged that KLFs exert complicated effects on cell proliferation, differentiation, survival, and responses to stimuli. Dysregulation of KLFs is associated with a range of diseases including cardiovascular disorders, metabolic diseases, autoimmune conditions, cancer, and neurodegenerative diseases. Their multidimensional roles in modulating critical pathways underscore the significance in both physiological and pathological contexts. Recent research also emphasizes their crucial involvement and complex interplay in the skeletal system. Despite the substantial progress in understanding KLFs and their roles in various cellular processes, several research gaps remain. Here, we elucidated the multifaceted capabilities of KLFs on body health and diseases via various compliable signaling pathways. The associations between KLFs and cellular energy metabolism and epigenetic modification during bone reconstruction have also been summarized. This review helps us better understand the coupling effects and their pivotal functions in multiple systems and detailed mechanisms of bone remodeling and develop potential therapeutic strategies for the clinical treatment of pathological diseases by targeting the KLF family.

Frontier and hotspot evolution in cerebrotendinous xanthomatosis: a bibliometric analysis from 1993 to 2023.

Background: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disease associated with lipid metabolic disorders. Because of its clinical diversity and rarity, the diagnosis is often unclear. However, there is still a lack of reports on bibliometric analysis of CTX. The aim of this study was to assess the progress and research developments of CTX over the past three decades, identify emerging trends, and establish novel directions for future research. Methods: The eligible literature were screened from the Web of Science Core Collection (WoSCC) database. The annual publication, countries, institutions, authors, journals, keywords and references were visually analyzed by Microsoft Excel 2019, CiteSpace 6.2.R4, VOSviewer 1.6.18 and online bibliometrics website (https://bibliometric.com/). Results: A total of 561 publications from WoSCC were included in this study. The United States is the country with the largest number of publications, and Karolinska Institutet is the institution with the largest number of publications. Björkhem I. ranks as the most published and cited author in the last three decades. Journal of Lipid Research is the most widely published and cited journal. The strongest burst of keywords is "diagnosis." Conclusion: Unraveling the pathogenesis of CTX and improving its diagnosis and treatment continue to be critical challenges that require urgent attention. Future research endeavors will be centered on enhancing the efficiency and accuracy of early diagnosis and intervention.

Analysis of risk factors and development of a nomogram prediction model for renal tubular acidosis in primary Sjogren syndrome patients.

OBJECTIVE: To investigate the risk factors of renal tubular acidosis (RTA) in patients with primary Sjögren's syndrome (pSS) and create a personalized nomogram for predicting pSS-RTA patients. METHOD: Data from 99 pSS patients who underwent inpatient treatment at our hospital from January 2012 to January 2024 were retrospectively collected and analyzed. Bootstrap resampling technique, single-factor, and multi-factor logistic regression analyses were used to explore the risk factors for pSS-RTA. A nomogram was developed based on the results of the multivariate logistic model. The model was evaluated through receiver operating characteristic curve, C-index, calibration curve, and decision curve analysis. In addition, we graded the severity of pSS-RTA patients and used univariate analysis to assess the relationship between pSS-RTA severity and risk factors. RESULTS: A multivariate logistic regression analysis revealed that concurrent thyroid disease, long symptom duration, subjective dry mouth, and positive RF were independent risk factors for pSS-RTA patients. Based on them, a personalized nomogram predictive model was established. With a p-value of 0.657 from the Hosmer-Lemeshow test, the model demonstrated a good fit. The AUC values in the training and validation groups were 0.912 and 0.896, indicating a strong discriminative power of the nomogram. The calibration curves for the training and validation groups closely followed the diagonal line with a slope of 1, confirming the model's reliable predictive ability. Furthermore, the decision curve analysis showed that the nomogram model had a net benefit in predicting pSS-RTA, emphasizing its clinical value.This study did not find an association between the severity of pSS-RTA and risk factors. DISCUSSION: We developed a nomogram to predict RTA occurrence in pSS patients, and it is believed to provide a foundation for early identification and intervention for high-risk pSS patients.

Short-term Outcome of RPVBT Combined with Chemotherapy for Patients with Single, < 3 cm, T2 Stage Bladder cancer.

BACKGROUND: To investigate the survival outcome of "radical" GreenLight photoselective vaporization of bladder tumor (RPVBT) in conjunction with postoperative chemotherapy for patients with single, < 3 cm in diameter, T2 stage muscle invasive bladder cancer (MIBC). METHODS: Thirty-eight patients with single, < 3 cm, T2 stage bladder cancer were treated with RPVBT combined with chemotherapy and were included in the RPVBT group. To compare the differences in survival outcome, 80 patients with Ta/T1 bladder cancer and 30 patients with T2 bladder cancer were included as controls. The 80 patients with Ta/T1 bladder cancer underwent GreenLight photoselective vaporization of bladder tumors(PVBT), while 30 patients with T2 bladder cancer underwent radical cystectomy (RC) combined with pelvic lymph node dissection (PLND). Tumor recurrence and death were recorded, and recurrence-free survival (RFS) and overall survival (OS) curves were plotted to compare the survival difference between the RPVBT and control groups. RESULTS: No significant differences were observed in comorbidities or living habits between the RPVBT and control groups. Blood loss [RPVBT: 20 (IQR10, 20) vs. RC: 100 (IQR90, 150) mL] and postoperative hospital stay [RPVBT: 5.5 (IQR5, 6), vs. RC: 10 (IQR8, 12) days] in the RPVBT group were significantly lower than that in the RC group. Urinary tract infection [RPVBT: 6 (15.8%) vs. PVBT: 14 (17.5%)] and bladder irritation sign [RPVBT: 11 (28.9%) vs. PVBT: 23 (28.8%) ] were the most common short-term complications in the RPVBT group, with no statistical difference between the RPVBT and PVBT group. The median follow-up time for survival endpoints was 22 (16, 27) months for the included patients after surgery. The outcomes of tumor recurrence at 12, 24, and 36 months were 2 (5.3%), 3 (7.9%), and 5 (13.2%) patients in the RPVBT groups, 13 (16.3%) and 3 (10%) patients experienced recurrence in the PVBT and RC groups at 36 months. No significant differences were noted among the three groups (P = 0.778). Additionally, Kaplan-Meier survival analysis revealed no statistically significant differences in RFS (P = 0.791) and OS (P = 0.689) among the three groups. CONCLUSIONS: Our findings indicate that RPVBT combined with chemotherapy is a simple and feasible treatment option with fewer complications and satisfactory survival outcomes in patients with single, < 3 cm, T2 stage bladder cancer.

Enhanced dielectric constant and breakdown strength of sandwiched polymer nanocomposite film for excellent energy storage.

Enhanced dielectric constant and high breakdown strength offers immense promise for excellent energy storage performance, which is of critical significance in modern electronics and power systems. However, polymer nanocomposites with traditional routes have to balance between dielectric constant and breakdown strength, hence hindering substantive increases in energy density. Herein, a sandwiched polymer nanocomposite film has been constructed to take full advantage of the individual component layers. BaTiO3 nanoparticles are coated with a fluoropolymer to form core-shell structures and then introduced into a polymer as the top and the bottom layers of a sandwich film for enhancing polarization. Moreover, boron nitride nanosheets (BNNSs) in the middle layer of the sandwich film exert positive effects on the inhibition of current leakage for high breakdown resistance. The breakdown strength increases from 480 MV m-1 of the neat polymer to 580 MV m-1 of the sandwiched film. Additionally, the film exhibits a higher dielectric constant in comparison with the neat polymer. The sandwiched film displays a superior energy density (15.75 J cm-3), which is about 1.9 times that of the neat polymer. This work proposes a feasible route to achieve excellent energy storage of polymer dielectrics by synergistically introducing insulating fillers and additional dipoles in a sandwiched polymer nanocomposite film.

Association between physical activity and visceral adiposity index (VAI) in U.S. population with overweight or obesity: a cross-sectional study.

BACKGROUND: Previous studies have revealed the effects of different physical activity (PA) types on visceral adipose tissue (VAT) accumulation in individuals with overweight/obesity. However, the independent association (especially the dose-response relationship) between PA and VAT in individuals with and without overweight/obesity remains less explored. Visceral adiposity index (VAI), calculated from waist circumference, body mass index (BMI), triglyceride and high-density lipoprotein cholesterol, is a novel indicator of VAT. This study aims to elucidate the association between PA and VAI in participants with and without overweight/obesity. METHODS: Participants who are overweight or obese and with complete data on VAI, PA, and other essential covariates from the National Health and Nutrition Examination Survey (NHANES) database (2015-2018) were included in this study. PA was evaluated by the PA questionnaire and converted into metabolic equivalent task (MET) hours per week (MET-h/wk) based on the suggested MET scores. Multivariate linear regression models were used to identify the association between PA and VAI. Subgroup analyses, combined with interaction tests and restricted cubic spline (RCS) regression analyses, were utilized to explore the stability and nonlinearity of PA-VAI association, respectively. RESULTS: A total of 4, 312 participants with complete data on PA and VAI was included in this study, with 3, 441 of them being overweight or obese. After adjusting for all potential covariates, increased PA was found to be significantly associated with remarkable lower level of VAI in all participants (ß = -0.0004, P = 0.003), participants with (ß = -0.0013, P = 0.012) and without (ß = -0.0004, P = 0.003) overweight/obesity. Subgroup analyses and interaction tests revealed that the PA-VAI association was not modified by other covariates in individuals with overweight/obesity. Furthermore, RCS analyses revealed that PA was significantly, linearly and negatively associated with VAI in all participants, participants with and without overweight/obesity (all P < 0.05, all P for nonlinearity > 0.05). Noteworthily, as opposed to individuals without overweight/obesity, PA was significantly associated with lower VAI in participants with overweight/obesity after exceeding the threshold of 150 MET-h/wk. CONCLUSION: Increased PA was significantly associated with lower level of VAI, but a higher level of PA (> 150 MET-h/wk) was needed to obtain significantly lower level of VAI in individuals with overweight/obesity.

Global burden of metabolic diseases, 1990-2021.

BACKGROUND: Common metabolic diseases, such as type 2 diabetes mellitus (T2DM), hypertension, obesity, hypercholesterolemia, and metabolic dysfunction-associated steatotic liver disease (MASLD), have become a global health burden in the last three decades. The Global Burden of Disease, Injuries, and Risk Factors Study (GBD) data enables the first insights into the trends and burdens of these metabolic diseases from 1990 to 2021, highlighting regional, temporal and differences by sex. METHODS: Global estimates of disability-adjusted life years (DALYs) and deaths from GBD 2021 were analyzed for common metabolic diseases (T2DM, hypertension, obesity, hypercholesterolemia, and MASLD). Age-standardized DALYs (mortality) per 100,000 population and annual percentage change (APC) between 1990 and 2021 were estimated for trend analyses. Estimates are reported with uncertainty intervals (UI). RESULTS: In 2021, among five common metabolic diseases, hypertension had the greatest burden (226 million [95 % UI: 190-259] DALYs), whilst T2DM (75 million [95 % UI: 63-90] DALYs) conferred much greater disability than MASLD (3.67 million [95 % UI: 2.90-4.61]). The highest absolute burden continues to be found in the most populous countries of the world, particularly India, China, and the United States, whilst the highest relative burden was mostly concentrated in Oceania Island states. The burden of these metabolic diseases has continued to increase over the past three decades but has varied in the rate of increase (1.6-fold to 3-fold increase). The burden of T2DM (0.42 % [95 % UI: 0.34-0.51]) and obesity (0.26 % [95 % UI: 0.17-0.34]) has increased at an accelerated rate, while the rate of increase for the burden of hypertension (-0.30 % [95 % UI: -0.34 to -0.25]) and hypercholesterolemia (-0.33 % [95 % UI: -0.37 to -0.30]) is slowing. There is no significant change in MASLD over time (0.05 % [95 % UI: -0.06 to 0.17]). CONCLUSION: In the 21st century, common metabolic diseases are presenting a significant global health challenge. There is a concerning surge in DALYs and mortality associated with these conditions, underscoring the necessity for a coordinated global health initiative to stem the tide of these debilitating diseases and improve population health outcomes worldwide.

A Bioinformatic Strategy for Investigating the Mechanism of Hispolon in the Treatment of Triple-Negative Breast Cancer Combined with In vitro Experiments.

BACKGROUND: Hispolon, a phenolic compound isolated from the medicinal yellow fungal mulberry, exhibits a strong anti-triple-negative breast cancer (TNBC) effect. However, the antitumor mechanisms of Hispolon have not been fully explored. OBJECTIVE: In this study, we systematically investigated the mechanism of Hispolon against TNBC based on bioinformatics and in vitro experiments. METHODS: The Hispolon-related targets were first collected from the SwissTarget database. Differential Expression Genes (DEG) were screened between TNBC and normal breast tissue using the Gene Expression Comprehensive (GEO) dataset. The overlapping targets between Hispolon and DEG were analyzed by plotting Venn maps. Protein-protein interaction (PPI) network was constructed to analyze the interactions among these targets. The focus was on mining the core targets of anti-TNBC effects of Hispolon via the Cytohubba and MCODE plugin of Cytoscape 3.7.2 software. We performed survival analysis on these core targets to screen the best-matched targets, including EGFR, KIT, and PLAU. This correlated strongly with our validation of Hispolon by molecular docking. In addition, Gene Ontology (GO) anal-ysis and KEGG pathway analysis were performed using R software (ClusterProfiler package). Finally, in vitro experiments were performed to assess the accuracy of predicted target genes. RESULTS: The ADME results suggested that Hispolon has great potential to develop into a drug. Twenty overlapping targets were screened by matching the 107 targets of Hispolon to the 2,013 targets of TNBC DEG. Seven core targets of Hispolon against TNBC were initially identified, including EGFR, IGFBP3, MMP9, MMP2, MMP1, PLAU, and KIT. GO enrich-ment analysis demonstrated that the biological process of Hispolon acting on TNBC mainly involves lymphocyte activation in immune response and phosphatidylinositol-mediated signal-ing. Additionally, the relaxin signaling pathway, estrogen signaling pathway, proteoglycans in cancer, and others might be the key pathways of Hispolon against TNBC. Furthermore, Hispo-lon inhibited the proliferation of MDA-MB-231 cells in a concentration-dependent manner and regulated the RNA and protein expression of the core targets EGFR, PLAU, and KIT for the treatment of TNBC. CONCLUSION: In this study, the polygenic pharmacological mechanism of action of Hispolon against TNBC was explored through network pharmacology and in vitro experiments, provid-ing a new insight into the mechanism of TCM monomer against TNBC.

Associations of childhood and adulthood body size, and child-to-adult body size change with adult telomere length.

AIM: To comprehensively examine the associations of childhood and adulthood body size, and child-to-adult body size change with adult leucocyte telomere length (LTL). METHODS: We included 453 602 participants from the UK Biobank. Childhood body size at the age of 10 years was collected through a questionnaire. Adulthood body size was assessed using body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fat mass index (FMI), and fat-free mass index (FFMI). RESULTS: Individuals with plumper body size in childhood exhibited shorter LTL in adulthood (-0.0086 [-0.0017, -0.0004]). Adulthood BMI (-0.0286 [-0.0315, -0.0258]), WC (-0.0271 [-0.0303, -0.0238]), WHR (-0.0269 [-0.0308, -0.0230]) and FMI (-0.0396 [-0.0438, -0.0351]) were negatively associated with LTL, whereas FFMI (0.0095 [0.0039, 0.0152]) was positively associated with LTL. Compared to individuals consistently having an average/normal weight in both childhood and adulthood, those who maintained or developed overweight/obesity from childhood to adulthood had a shorter adult LTL, regardless of childhood body size. Notably, the LTL shortening effect was not observed in individuals with plumper body size in childhood but normal weight in adulthood. CONCLUSIONS: Childhood and adulthood obesity are both associated with LTL shortening in adulthood. Transitioning to or maintaining overweight/obese status from childhood to adulthood is associated with shorter adult LTL, whereas this effect can be reversed if plumper children become normal weight.

LL-37 and bisphosphonate co-delivery 3D-scaffold with antimicrobial and antiresorptive activities for bone regeneration.

This study introduces a novel 3D scaffold for bone regeneration, composed of silk fibroin, chitosan, nano-hydroxyapatite, LL-37 antimicrobial peptide, and pamidronate. The scaffold addresses a critical need in bone tissue engineering by simultaneously combating bone infections and promoting bone growth. LL-37 was incorporated for its broad-spectrum antimicrobial properties, while pamidronate was included to inhibit bone resorption. The scaffold's porous structure, essential for cell infiltration and nutrient diffusion, was achieved through a freeze-drying process. In vitro assessments using SEM and FTIR confirmed the scaffold's morphology and chemical integrity. Antimicrobial efficacy was tested against pathogens of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). In vivo studies in a murine model of infectious bone defect revealed the scaffold's effectiveness in reducing inflammation and bacterial load, and promoting bone regeneration. RNA sequencing of treated specimens provided insights into the molecular mechanisms underlying these observations, revealing significant gene expression changes related to bone healing and immune response modulation. The results indicate that the scaffold effectively inhibits bacterial growth and supports bone cell functions, making it a promising candidate for treating infectious bone defects. Future studies should focus on optimizing the release of therapeutic agents and evaluating the scaffold's clinical potential.

Reproductive factors, genetic susceptibility and risk of type 2 diabetes: A prospective cohort study.

AIM: To explore the relationships of multiple reproductive factors with type 2 diabetes mellitus (T2DM) risk and the joint effects of reproductive factors and genetic susceptibility. METHODS: We included 262,368 women without prevalent T2DM from the UK biobank. Cox proportional hazards regression models were employed to estimate the relationships of reproductive factors with T2DM risk and the joint effects of reproductive factors and genetic susceptibility. RESULTS: During a mean follow-up of 12.2 years, 8,996 T2DM cases were identified. Early menarche (<12 years, hazard ratio (HR) 1.08 [95 % confidence interval (CI) 1.02;1.13]), late menarche (≥15 years, HR 1.11 [1.04;1.17]), early menopause (<45 years, HR 1.20 [1.12;1.29]), short reproductive lifespan (<30 years, HR 1.25 [1.16;1.35]), hysterectomy (1.31, HR [1.23;1.40]), oophorectomy (HR 1.28 [1.20;1.36]), high parity (≥4, HR 1.25 [1.17;1.34]), early age at first live birth (<20 years, HR 1.23 [1.16;1.31]), miscarriage (HR 1.13 [1.07;1.19]), stillbirth (HR 1.14 [1.03;1.27]), and ever used hormonal replacement therapy (HR 1.19 [1.14;1.24]) were related to a higher T2DM risk, while ever used oral contraceptives (HR 0.93 [0.89;0.98]) was related to a lower T2DM risk. Furthermore, women with reproductive risk factors and high genetic risk had the highest T2DM risk compared to those with low genetic risk and without reproductive risk factors. CONCLUSION: Our findings show that multiple reproductive factors are related to T2DM risk, particularly in women with high genetic risk.

Does androgenic alopecia aggravate the risk of prostate cancer? Evidence from Mendelian randomization.

Background: Epidemiological reports indicate a potential association between androgenic alopecia (AGA) and increased prostate cancer (PC) prevalence, but conflicting reports also exist. This study aims to elucidate the causality of AGA on PC risk using Mendelian randomization (MR) analysis. Materials and methods: Two-sample MR analyses utilized public genome-wide association studies summary data for single-nucleotide polymorphisms associated with AGA. Four statistical methods were used: inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode, with IVW as the preliminary estimation method. Additionally, sensitivity analyses were conducted to address pleiotropic bias. Results: Genetically proxied AGA did not demonstrate a causal effect on PC risk (IVW P > 0.05). Consistently, complementary methods yielded results aligned with IVW. Conclusions: Our MR analysis indicates no causal relationship between genetically predicted AGA and PC risk, suggesting that observed associations in epidemiological studies may not be causal.

Effect of saline perfusion before catheter removal in patients with BPH treated with GreenLight laser photoselective vaporization of the prostate.

OBJECTIVE: To investigate the effect of saline perfusion before catheter removal in patients with benign prostatic hyperplasia (BPH) treated with GreenLight laser photoselective vaporization of the prostate (PVP). MATERIALS AND METHODS: Patients (n=200) with BPH treated with PVP were divided into perfusion (n=100) and control (n=100) groups. For the perfusion group, saline (200 mL or the maximum capacity tolerated) was irrigated into the bladder after standardized external urethral disinfection, and the catheter was removed. Catheter removal was routinely performed in the control group. Perioperative adverse events and clinical outcomes were compared between the groups. RESULTS: Patients in the perfusion group had a shorter waiting time [3 (0-4) vs. 15 (8.75-26) min; P<0.001] and a better satisfaction grade [24 (21.75-26) vs. 23 (20-25); P=0.016] for first urination than those in the control group. The perfusion group exhibited lower anxiety levels regarding first urination than the control group [1 (1-2) vs. 1.5 (1-2), respectively; P=0.012]. Urinalysis revealed that the perfusion group had significantly lower white blood cell (WBC) count than the control group on the day [25.5 (8-37.75) vs. 43.5 (24.0-64.75); P<0.001] and 2 weeks [20.5 (11-27) vs. 31.0 (20-42); P<0.001] after catheter removal. No significant differences in treatment-related adverse events were observed [perfusion (n=15), control (n=20)]. CONCLUSION: Saline perfusion before catheter removal in patients with BPH treated with PVP could shorten the waiting time for first urination, improve patient anxiety and satisfaction and reduce postoperative urinary WBC levels.

Extraction of Astaxanthin from Haematococcus pluvialis and Preparation of Astaxanthin Liposomes.

Astaxanthin has 550 times more antioxidant activity than vitamin E, so it can scavenge free radicals in vivo and improve body immunity. However, the poor stability of astaxanthin becomes a bottleneck problem that limits its application. Herein, Haematococcus pluvialis (H. pluvialis) as a raw material was used to extract astaxanthin, and the optimal extraction conditions included the extraction solvent (EA:EtOH = 1:6, v/v), extraction temperature (60 °C), and extraction time (70 min). The extracted astaxanthin was then loaded using lecithin to form corresponding liposomes via the ethanol injection method. The results showed that the particle size and zeta potential of the prepared liposomes were 105.8 ± 1.2 nm and -38.0 ± 1.7 mV, respectively, and the encapsulation efficiency of astaxanthin in liposomes was 88.83%. More importantly, the stability of astaxanthin was significantly improved after being embedded in the prepared liposomes.